Giant Migrating Contractions Research Articles

Involvement of the autonomic nervous system in colonic contractions in conscious Suncus murinus.

Colonic motility is regulated by various factors along the gut-brain axis; however, detailed mechanisms are unknown. This study aimed to examine the involvement of the autonomic nervous system in colonic motility. Suncus murinus (suncus) is a small laboratory mammal suitable for gastrointestinal motility studies. Colonic motility and concomitant feeding and defecation behaviors in vagotomized and reserpine-administered suncus were recorded simultaneously for 24 h. Furthermore, we performed immunohistochemistry on tyrosine hydroxylase (TH) and insitu hybridization on corticotropin-releasing hormone (CRH) in suncus brain. Additionally, we examined c-Fos expression in the brain using immunohistochemistry in conscious suncus with colorectal distension. In vagotomized suncus, clustered giant migrating contractions (GMCs), consisting of strong contractions occurring in a short time, were observed, and the percentage of GMCs without defecation increased. The frequency of GMCs in the reserpine-administered suncus increased during a light period (ZT0-4, 4-8) and decreased during a dark period (ZT16-20, 20-24) compared to a vehicle group. Additionally, the percentage of GMCs without defecation in the reserpine-administered suncus increased. Suncus TH-immunopositive neurons were found in the locus coeruleus (LC), as shown in rodents. In contrast, CRH mRNA-expressing cells were not observed in a region assumed to be the Barrington's nucleus (Bar). Furthermore, colorectal distension in conscious suncus induced c-Fos expression in LC TH neurons. Our results suggest that the vagus and sympathetic nerves are not required for induction of GMCs invivo. However, they are likely to exert a modulatory role in control of GMC frequency in Suncus murinus.

Diurnal changes of colonic motility and regulatory factors for colonic motility in Suncus murinus.

The aim of this study was to investigate the fundamental mechanisms of colonic motility in the house musk suncus (Suncus murinus) as an established animal model of gut motility. To measure gut motility in free-moving conscious suncus, strain gauge force transducers were implanted on the serosa of the colon and gastric body. We recorded diurnal changes in colonic motility and observed the relationship between feeding and colonic motility. Giant migrating contractions (GMCs) of the colon were invariably detected during defecation and tended to increase during the dark period, thereby indicating that colonic motility has a circadian rhythm. Given that GMCs in the suncus were observed immediately after feeding during the dark period, we assume the occurrence of a gastrocolic reflex in suncus, similar to that observed in humans and dogs. We also examined the factors that regulate suncus GMCs. Intravenous administration of 5-HT (100µg/kg), substance P (10 and 100µg/kg), calcitonin gene-related peptide (10µg/kg), and α2 adrenergic receptor antagonist yohimbine (0.5, 1, and 3mg/kg) induced GMC-like contractions, as did intragastric and intracolonic administration of the transient receptor potential vanilloid 1 agonist, capsaicin (1mg/kg). These results indicate that the fundamental mechanisms of colonic motility in suncus are similar to those in humans and dogs, and we thus propose that suncus could serve as a novel small animal model for studying colonic motility.

Thyroid hormone activated upper gastrointestinal motility without mediating gastrointestinal hormones in conscious dogs

This study was conducted to clarify the relationship between thyroid function and gastrointestinal motility. We established an experimental configuration in which the feedback of thyroid function was completely removed using conscious dogs. With hypothyroidism, time of phase I of interdigestive migrating contractions (IMC) was longer, time of phase II and phase III was significantly shortened, and both the continuous time of strong tetanic contraction at antrum and 10-h frequency of phase III counted from the first IMC after meal significantly decreased. Whereas, hyperthyroidism caused the opposite events to those with hypothyroidism. Furthermore, We found giant migrating contractions (GMC) occurred from the upper gastrointestinal tract when we administrated high dose of thyroid hormone. One GMC occurred from anal sides propagated to cardiac, and this propagation was similar to the emesis-like interdigestive motor activity, the other GMC occurred from oral sides propagated to anal sides and this was similar to the diarrhea-like interdigestive motor activity. We examined the relationship between thyroid function and gastrointestinal hormones including of ghrelin, GLP-1, and cholecystokinin (CCK). However, we could not find significant differences under different thyroid hormone status. This is the first report that thyroid hormone activated upper gastrointestinal motility without mediating gastrointestinal hormones.

Elobixibat, an ileal bile acid transporter inhibitor, induces giant migrating contractions during natural defecation in conscious dogs.

Chronic constipation affects 14%-17% of the population. Elobixibat, a novel, ileal bile acid transporter (IBAT) inhibitor, has been approved as a new chronic constipation drug in Japan in January 2018. The present study aimed to examine the pharmacological effects of elobixibat on colonic motility in conscious dogs using a telemetry system. Six male beagle dogs were surgically implanted with strain gauge force transducers for gastrointestinal (GI) motility recording. The motility index was calculated from GI motility at each recording site in conscious and nonrestraint dogs. The fasted dogs were orally administered elobixibat (3, 10, or 30mg kg-1 ) or 30mg kg-1 of sennoside as positive control or vehicle using a crossover design and washout period of more than 6days. One hour after drug administration, the dogs were fed chow, and GI motility and defecation were observed for 10hours; GI motility was quantified to calculate giant migrating contractions (GMCs). Fecal bile acids (BAs) were determined as well. Elobixibat and sennoside significantly increased the number of defecations, fecal wet weight, and water content within 10hours after administration. Elobixibat dose-dependently decreased the time to first bowel movement, increased the amount of total fecal BAs, and rapidly induced mild GMCs during defecation; however, higher strength of GMCs was observed with sennoside. Elobixibat induces bowel movements faster than sennoside through a different mechanism. Elobixibat locally inhibits IBAT in the ileal lumen, leading to elevated fecal BAs in the colon and induced mild GMCs during defecation.

Effects of Calcitonin Gene-Related Peptide on Colonic Motility and Defecation in Conscious Dogs

BackgroundAlthough intra-arterial infusion of calcitonin gene-related peptide (CGRP) reportedly stimulates giant migrating contractions (GMCs) of the small intestine in conscious dogs, the effect of intravenous CGRP administration on colonic motility remains unclear. In the present study, we investigated the effects of intravenous CGRP on colonic motility and defecation and determined the underlying mechanism of action in conscious dogs. MethodsSixteen Beagle dogs weighing 11–13 kg were included. The effects of intravenous CGRP at doses of 3.33 (with various antagonists), 0.83, and 1.67 μg/kg on colonic motility and defecation were evaluated in neurally intact dogs (n = 6). For comparison, dogs with transection/re-anastomosis (T/R) between the proximal and middle segments of the colon (n = 5) and dogs with extrinsic denervation of the ileocolonic segments (n = 5) also received intravenous CGRP at 3.33 μg/kg. All dogs were equipped with strain gauge force transducers on the ileocolon for measurement of the colonic contractile activity. ResultsIntravenous CGRP evoked GMCs and defecation in the neurally intact group; these stimulatory effects were inhibited by atropine and hexamethonium. Compared with the neurally intact group, the T/R group exhibited similar proximal colonic motility and decreased distal colonic motility after intravenous CGRP administration, whereas the extrinsic denervation group exhibited increased colonic motility overall. ConclusionsIntravenous CGRP induces colonic motility and defecation through acetylcholine release in conscious dogs. The continuity of the enteric nerves plays an important role in CGRP-induced colonic contractions and defecation, while the extrinsic nerves suppress CGRP-induced colonic motility.

DSP-6952, a novel 5-HT4 receptor partial agonist, inhibits visceral hypersensitivity and ameliorates gastrointestinal dysfunction in experimental animals

The pharmacological profile of DSP-6952, a novel 5-HT4 receptor partial agonist, was investigated to evaluate the potential use for GI disorders, and to compare its effects in some GI dysfunction models with those of clinically efficacious prokinetic agents. DSP-6952 enhanced gastric motility and caused colonic giant migrating contractions (GMCs) associated with defecation in conscious dogs, having ED50 value for inducing GMCs of 1.56 mg/kg. DSP-6952 (3–10 mg/kg, i.g.) significantly enhanced colonic transit rate in guinea pigs; this enhancement was antagonized by SB-207266, a selective 5-HT4 receptor antagonist. DSP-6952 (1–10 mg/kg, p.o.) rapidly increased fecal wet weight without increasing fluid content in mice. Sennoside (30–100 mg/kg, p.o.) also increased fecal wet weight; however, it significantly increased fluid content with diarrhea. DSP-6952 dose-dependently improved clonidine- and morphine-induced delay in whole-gut transit in mice (ED50= 0.429 mg/kg and 0.310 mg/kg, respectively), which represented atonic and spastic constipation models, respectively. In viscerally hypersensitive rats treated with acetic acid, DSP-6952 (10 mg/kg, i.p., 30 mg/kg, p.o., 30 mg/kg, i.c.) and tegaserod (1 mg/kg, i.p.), but not prucalopride (10 mg/kg, i.p.), significantly inhibited the increase in colorectal distension-induced visceromotor response; these findings suggest that DSP-6952 and tegaserod inhibit visceral hypersensitivity in rats. It was concluded that DSP-6952, a novel and orally available 5-HT4 receptor agonist, induced colonic GMCs, enhanced colonic transit, increased defecation without inducing diarrhea, improved drug-induced delay in whole-gut transit, and inhibited visceral hypersensitivity in experimental animals. Therefore, DSP-6952 is expected to become a useful drug for treatment of IBS-C and chronic constipation.

Intracolonic Administration of the TRPA1 Agonist Allyl Isothiocyanate Stimulates Colonic Motility and Defecation in Conscious Dogs

BackgroundThe aim of the present study was to investigate the effects of the intracolonic transient receptor potential (TRP) A1 agonist allyl isothiocyanate (AITC) on colonic motility and defecation. MethodsThe effects of AITC administered into the proximal colonic lumen on colonic motility and defecation were studied in neurally intact dogs equipped with strain-gauge force transducers on the colon, with or without various antagonists. Effects of intracolonic AITC were also studied in dogs with either transection/re-anastomosis (T/R) between the proximal and middle colon and complete extrinsic denervation of an ileocolonic segment. ResultsAITC increased colonic motility and induced giant migrating contractions (GMCs) with defecations in 75 % of experiments in neurally intact dogs. These effects were inhibited by atropine, hexamethonium, ondansetron, and HC-030031 but unaltered by capsazepine. In dogs with T/R, the increase in colonic motility was inhibited in the middle-distal colon. In dogs with extrinsic denervation, the increase in colonic motility in the distal colon was decreased. ConclusionsIntracolonic AITC stimulates colonic motility and defecation via cholinergic, serotonergic, and TRPA1 pathways. Continuity of colonic enteric neurons plays an essential role in the intracolonic AITC-induced colonic motor response, while extrinsic nerves are important in occurrence and propagation of GMCs.

Treatment of IBS-D with 5-HT3 receptor antagonists vs spasmolytic agents: similar therapeutical effects from heterogeneous pharmacological targets

There is still no agreement over optimal pharmacological treatment for irritable bowel syndrome (IBS). Patients with IBS and diarrhea (IBS-D) demonstrate both visceral hypersensitivity and impaired colonic motility with increased frequency and amplitude of giant migrating contractions (GMCs) which cause mass movements, propulsion of stools and initiation of defecation. Both antispasmodics and 5-HT3 receptor antagonists can improve the symptoms and the impaired colonic motility of patients with IBS-D though through very different mechanisms. Antispasmodics act by directly relaxing the colonic smooth muscle cells or antagonizing the excitatory neuromuscular neurotransmission. In contrast, the mechanism of action of 5HT3 antagonists is much more complex and subtle as they inhibit the ascending excitatory component of the peristaltic reflex and GMCs. There are some concerns about the safety of 5HT3 antagonists in long-term treatment. Most of the studies on the treatment of IBS have followed the pharmacological strategy of looking for big clinical effects acting on a single receptor/target. We propose a pharmacologic strategy which uses different drugs for pain and dysmotility in the same patient and includes specific drugs acting on smooth muscle cells, neuromuscular transmission, synaptic transmission and intrinsic afferents. The clinical effect on IBS symptoms would be found in the sum of all these smaller effects on multiple targets.

Propagation of giant migrating contractions between the small intestine, cecum and colon during radiation

Radiation increases the frequency of small intestinal and colonic giant migrating contractions (GMCs). These contractions contribute to the diarrhea and cramping after radiation therapy and are coordinated with one another across the ileocolonic (IC) junction. We investigated the coordination of contractile activity between the small intestine, cecum and colon in five canines following circumferential myotomy on the ileum at the IC junction and compared it to intact animals. Studies were performed before and during a radiation schedule. Myotomy increased the frequency of small intestinal GMCs prior to irradiation. In intact animals, the duration and amplitude of cecal GMCs decreased when multiple contractions occurred in rapid succession. This is in contrast to small intestinal and colonic GMCs and suggests a different mechanism of propagation for GMCs within the cecum. Ileal myotomy dramatically decreased the frequency of propagating radiation-induced colonic GMCs. The total number of colonic GMCs was not altered. Colonic contractile activity was disrupted in intact animals during irradiation. However, after ileal myotomy, irradiation did not affect the pattern of colonic contractile states. Diarrhea in irradiated animals with myotomy started earlier than intact animals. This may be related to the frequency of small intestinal GMCs. Our findings suggest importance of the enteric neural connections at the IC region to contractile disorders of both the small and large intestine. The anatomic relationship between the canine IC junction is similar to the human ileo-appendiceal-colonic region and surgical manipulations of this area may likewise affect human contractile activity.

Characterization of special propulsive contractions during rectal evacuation in a canine model of intestinal extrinsic denervation and rectal transection

The mechanism for the initiation of giant migrating contractions (GMCs) associated with defecation is not well known. The aim of this study was to describe the characteristics of special propulsive contractions (SPCs), such as GMCs, during evacuation in four experimental dog models, with emphasis on denervation. Twenty healthy dogs were used in this study, and they were divided into four groups, i.e., control (underwent force transducer implantation alone), denervation (underwent transection of the descending nerve fibers along the caudal mesenteric artery (CMA)), transection (underwent transection of the rectum, which corresponds to transection of the enteric nerve fibers), and denervation-plus-transection (underwent transection of the descending nerve fibers along the CMA and transection of the rectum). Colonic contractile activities were continuously recorded on a computer. Five force transducers were implanted at the serosal surfaces of the colon (C1-R). The consistency of dog feces was checked daily. The parameters of rectal relaxation (RR), defecation characteristics, and SPCs, such as motility index (MI), duration, and frequency, were measured. In the control and denervation groups, GMCs were observed with evacuation, and RR occurred synchronously with the initiation of GMCs. On the other hand, in the transection and denervation-plus-transection groups, strong force contractions without RR occurred only during evacuation. The MI and duration of the transection and denervation-plus-transection groups were higher than those of other groups (p < 0.05). The frequency of SPCs was the highest in the denervation-plus-transection group. In conclusion, the continuity of enteric nerves is necessary for the occurrence of GMCs and rectal relaxation (RR).

Stimulatory action of mitemcinal (GM‐611), an acid‐resistant non‐peptide motilin receptor agonist, on colonic motor activity and defecation: spontaneous and mitemcinal‐induced giant migrating contractions during defecation in dogs

The aim of this study was to characterize giant migrating contractions (GMCs) during spontaneous defecation in dogs and to investigate the effect of mitemcinal (an orally active and highly acid-resistant motilin receptor agonist) on colonic motility to assess the possibility of using it for the treatment of colonic motility disorders. To assess colonic motility, strain-gauge force transducers were implanted on the gastrointestinal tract of five dogs, and the behaviour of the dogs was monitored with a noctovision-video camera system. The effect of mitemcinal (0, 3, 10 or 30 mg per dog) and sennoside (300 mg per dog) on colonic motility was assessed 24 h after oral administration. During a 39-day period, the starting point of most of the 140 GMCs was between the transverse colon and the descending colon, but some variation was observed. In the daytime, the GMCs originated from somewhat more proximal positions than at night. Mitemcinal caused an increase in the GMC-index (integration of contractile amplitude and duration) and proximal translocation of the GMC starting point, but did not cause an increase in the number of defecations 12 h after administration. Sennoside, however, caused a significant increase in the number of defecations, an increase in the GMC-index, and prolongation of the duration of GMCs. The GMC starting point in the canine colon varied during spontaneous defecation. Mitemcinal was a potent prokinetic drug to mimic a spontaneous defecation compared with sennoside. Mitemcinal evacuates more intestinal luminal contents during the defecation than does sennoside.

Cholinergic giant migrating contractions in conscious mouse colon assessed by using a novel noninvasive solid-state manometry method: modulation by stressors

There is a glaring lack of knowledge on mouse colonic motility in vivo, primarily due to unavailability of adequate recording methods. Using a noninvasive miniature catheter pressure transducer inserted into the distal colon, we assessed changes in colonic motility in conscious mice induced by various acute or chronic stressors and determined the neurotransmitters mediating these changes. Mice exposed to restraint stress (RS) for 60 min displayed distal colonic phasic contractions including high-amplitude giant migrating contractions (GMCs), which had peak amplitudes >25 mmHg and occurred at a rate of 15-25 h(-1) of which over 50% were aborally propagative. Responses during the first 20-min of RS were characterized by high-frequency and high-amplitude contractions that were correlated with defecation. RS-induced GMCs and fecal pellet output were blocked by atropine (0.5 mg/kg ip) or the corticotrophin releasing factor (CRF) receptor antagonist astressin-B (100 microg/kg ip). RS activated colonic myenteric neurons as shown by Fos immunoreactivity. In mice previously exposed to repeated RS (60 min/day, 14 days), or in transgenic mice that overexpress CRF, the duration of stimulation of phasic colonic contractions was significantly shorter (10 vs. 20 min). In contrast to RS, abdominal surgery abolished colonic contractions including GMCs. These findings provide the first evidence for the presence of frequent cholinergic-dependent GMCs in the distal colon of conscious mice and their modulation by acute and chronic stressors. Noninvasive colonic manometry opens new venues to investigate colonic motor function in genetically modified mice relevant to diseases that involve colonic motility alterations.

Effect of daily loperamide administration on gastrointestinal myoelectric activity

The objective of this study was to determine the effect of daily administration of loperamide on gastrointestinal myoelectric activity. Six dogs were randomly administered three regimens–placebo, low dose loperamide (0.10–0.15 mg/kg/day, p.o.), and high dose loperamide (0.30–0.36 mg/kg/day, p.o.)–for one week each. Using surgically implanted bipolar electrodes, gastrointestinal myoelectric activity was recorded on at least 2 fed and 2 fasted experimental days for each regimen. In the fasted state, low dose loperamide decreased MMC cycle length, initiated intestinal amyogenesia in 40% of experiments, but did not induce vomiting. High-dose loperamide in the fasted state did not change MMC cycle length, but induced vomiting in 50% of experiments and initiated intestinal amyogenesia in 43% of experiments. The rate of occurrence of the myoelectric carrelates of giant migrating contractions (GMCs) and retrograde giant contractions (RGCs) increased with loperamide administration at both doses, as did the rate of occurrence of fed state MMCs. We conclude that daily oral administration of loperamide results in: (1) a dose-dependent effect on MMC cycle length; (2) intestinal amyogenesia; (3) an increase in frequency of vomiting at higher doses; and (4) an increase in incidence of GMCs and RGCs.

Enteric descending and afferent neural signaling stimulated by giant migrating contractions: essential contributing factors to visceral pain

We investigated whether strong compression of an intestinal segment by giant migrating contractions (GMCs) initiates pseudoaffective signals from the gut, similar to those initiated by its distension with a balloon. The experiments were performed on conscious dogs by using close intra-arterial infusions of test substances that affect the receptors only in the infused segment. The stimulation of GMCs by close intra-arterial infusion of CGRP or distension of an intestinal segment by balloon increased the heart rate; the increase in heart rate was greater when the balloon distension and GMCs occurred concurrently in separate intestinal segments. The suppression of contractility in the distended segment blocked the increase in heart rate. By contrast, the stimulation of rhythmic phasic contractions (RPCs) or their spontaneous occurrence did not increase the heart rate. The occurrence of GMCs as well as intestinal distension also produced descending inhibition. The descending inhibition was blocked by the inhibition of nitric oxide synthase, but it was unaffected by the inhibition of adenylyl cyclase, purinergic receptors P2X and P2Y, and muscarinic receptors M(1) and M(2). The synaptic transmission for descending inhibition was mediated primarily by nicotinic receptors and activation of nitric oxide synthase. It was unaffected by the inhibition of tachykinin receptors NK(1), NK(2), and NK(3); serotonin receptors 5-HT(1A), 5-HT(2)/5-HT(1C), 5-HT(3), and 5-HT(4); and muscarinic receptors. Our findings show that GMCs, but not RPCs, initiate pseudoaffective signals from the gut. In the presence of visceral hypersensitivity or impaired descending inhibition, the GMCs may become a noxious stimulus.

Induction and recovery of colonic motility/defecatory disorders after extrinsic denervation of the colon and rectum in rats

Anterior resection for rectal disease is associated with extrinsic autonomic denervation of the neorectum, which may influence the myenteric plexus, and subsequently the motility/defecatory status after operation. A rat model with denervated neorectum was constructed. Colonic contractile activity in vivo, the amount of generic neuron marker (PGP 9.5) and nitric oxide synthase (NOS) were measured periodically. The responses of the muscle strip in each period to electrical field stimulation were evaluated using various neurotransmitters. In rats with denervated neorectum, giant migrating contractions (GMCs) of the distal colon, the number of fecal lumps per day and their small size, significantly increased in the early phase postoperatively, although both recovered in the late-phase period. The contractile response of the muscle strip of the denervated colon to acetylcholine was reduced throughout the period; however, contraction of the denervated colon under the addition of NO inhibitor (l-NAME) was enhanced significantly in the late-phase period, and recovered to the control level by atropine. Neuronal NOS, but not PGP 9.5 concentration, in the myenteric plexus at the distal denervated colon, significantly increased in the late-phase period. None of the above items differed from the control at other colonic portions throughout the period. Extrinsic autonomic denervation causes abnormal hyper-motility in the neorectum, which may be associated with multiple evacuations in the early phase postoperatively. Increased acetylcholine and the subsequent increase of neuronal NOS in the myenteric plexus may be an adaptive mechanism to compensate for such abnormal colonic motility after extrinsic denervation.

Neuronal locus and cellular signaling for stimulation of ileal giant migrating and phasic contractions.

We investigated the neuronal locus, the role of PKC activation, and utilization of extracellular Ca(2+) and intracellular Ca(2+) release in smooth muscle cells for the generation of giant migrating contractions (GMCs) and rhythmic phasic contractions (RPCs) in intact normal and inflamed canine ileum. Calcitonin gene-related peptide (CGRP), administered close intra-arterially, stimulated GMCs at higher doses and RPCs at smaller doses. These effects were blocked by prior close intra-arterial infusions of CGRP(8-37), atropine, hexamethonium, and TTX but not by tachykinin, serotonin, and histaminergic receptor subtype antagonists. Both types of contractions were blocked by verapamil in normal and inflamed ileums. Dantrolene and ruthenium red blocked only the RPCs in normal ileum but blocked both GMCs and RPCs in the inflamed ileum. PKC inhibition by chelerythrine blocked GMCs only in inflamed ileum but blocked RPCs in both normal and inflamed ileums. The inhibition of phospholipase C by neomycin blocked both RPCs and GMCs in normal and inflamed ileums. In conclusion, acetylcholine is the common neurotransmitter for the stimulation of both GMCs and RPCs, but the signaling cascades for their stimulation are partially divergent, and they differ also in the normal and inflamed states.

Cholinergic and nitrergic regulation of in vivo giant migrating contractions in rat colon.

The aim of this study was to characterize in vivo rat colonic motor activity in normal and inflamed states and determine its neural regulation. Circular muscle contractions were recorded by surgically implanted strain-gauge transducers. The rat colon exhibited predominantly giant migrating contractions (GMCs) whose frequency decreased distally. Only a small percentage of these GMCs propagated in the distal direction; the rest occurred randomly. Phasic contractions were present, but their amplitude was very small compared with that of GMCs. Inflammation induced by oral administration of dextran sodium sulfate suppressed the frequency of GMCs in the proximal and middle but not in the distal colon. Frequency of GMCs was suppressed by intraperitoneally administered atropine and 4-diphenylacetoxy-N-methyl-piperidine methiodide and was enhanced by N(w)-nitro-L-arginine methyl ester. Serotonin, tachykinin, and calcitonin gene-related peptide receptor or receptor subtype antagonists as well as guanethidine and suramin had no significant effect on the frequency of GMCs. Verapamil transiently suppressed the GMCs. In conclusion, unlike the canine and human colons, the rat colon exhibits frequent GMCs and their frequency is suppressed in inflammation. In vivo GMCs are stimulated by neural release of acetylcholine that acts on M3 receptors. Constitutive release of nitric oxide may partially suppress their frequency.

Differential signal transduction pathways to stimulate colonic giant migrating and phasic contractions

Differential signal transduction pathways to stimulate colonic giant migrating and phasic contractions

Experimental Study on Gastrointestinal Motility in Inflammatory Bowel Disease.

The symptoms of urgency, diarrhea and nausea are exhibited in inflammatory bowel disease such as ulcerative colitis. The correlation among the changes of motility in gastrointestinal tracts and the symptoms were investigated using a model of acute colitis in ten dogs. Colitis was induced by acetic acid and the motility in gastrointestinal tracts was recorded with strain gauge transducers. The dogs exhibited urgency and diarrhea with mucus and blood during colitis. At the same time, the motor activity of the colon and stomach changed during colitis: 1) the incidence of colonic motor complexes (CMCs) were significantly decreased ; 2) the total duration per hour and mean duration of CMCs also decreased significantly ; 3) the incidence of giant migrating contractions (GMCs) increased significantly ; and 4) interdigestive migrating complex (IMC) of the stomach was disrupted and changed to irregular pattern. The response of colonic motility to a meal during colitis was also investigated. As the result, 1) the incidence of CMCs had a tendency to increase in the early postprandial periods in the proximal and distal colon and 2) the incidence of GMCs had similar effects to the incidence of CMCs. These findings may indicate that Gastro-Colonic Response during colitis, similarly to the normal colon, remains. There was no significant difference between the cleansed and uncleansed colon during colitis or in the normal colon. On the other hand, there was significant shortening of the mouth to caecum transit time during colitis. In conclusion, the changes in gastric and colonic motor activity, including the shortening of the mouth to caecum transit time, may be related to the abdominal symptoms accompanied by acute colitis. Moreover, the change of colonic motility including CMCs and GMCs in the early postprandial period indicates a close correlation between worseing of abdominal symptoms and up-take of meal.

Ca2+ channel blockade by verapamil inhibits GMCs and diarrhea during small intestinal inflammation.

The aim of this study was to investigate whether the blockade of L-type Ca2+ channels with verapamil suppresses giant migrating contractions (GMCs) and therefore diarrhea during small intestinal inflammation. Small intestinal inflammation was induced by infection with the nematode Trichinella spiralis. T. spiralis infection alone significantly increased the frequency of GMCs and decreased the frequency of phase III activity in the small intestine for 9 days. The increased frequency of GMCs was associated with diarrhea. Immunohistochemical staining with specific antibodies indicated that the number of neutrophils and mast cells increased significantly in the jejunal lamina propria during T. spiralis infection. Only the neutrophils increased significantly in the muscularis externa of the jejunum. Myeloperoxidase (MPO) activity increased significantly in the jejunal and ileal lamina propria. Daily verapamil administration during T. spiralis infection significantly reduced the frequency of GMCs and diarrhea but had no further significant effect on the already reduced frequency of phase III activity. Verapamil administration, however, did not reduce MPO activity or immunocyte infiltration in the jejunum or ileum. We conclude that blockade of L-type Ca2+ channels selectively reduces the frequency of GMCs and therefore diarrhea during small intestinal inflammation. The decreased frequency of GMCs is not secondary to a reduction in the inflammatory response.